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Biomedical subjects

Nelson Lee

Publications and source records attributed to Nelson Lee.

At least 19 recordsLinked to original sources

Prospective comparison of three predictive rules for assessing severity of community-acquired pneumonia in Hong Kong.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong. AIM: To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6-point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65. METHODS: A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared. RESULTS: The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut-off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%). CONCLUSION: All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low-risk patients.

Adolescent↗

Assessing the genetic diversity of the aldolase genes of Plasmodium falciparum and Plasmodium vivax and its potential effect on performance of aldolase-detecting rapid diagnostic tests.

Malaria-specific rapid diagnostic tests (RDTs) targeting aldolase show highly variable sensitivities. We assessed diversity in Plasmodium falciparum and P. vivax aldolases by sequencing the coding genes from parasites of various origins. The results show that aldolases are highly conserved, indicating that antigenic diversity is not a cause of variable RDT sensitivity.

Aldehyde-Lyases↗

Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2 on binding of specific monoclonal antibodies: Implications for rapid diagnostic tests for malaria.

The ability to accurately diagnose malaria infections, particularly in settings where laboratory facilities are not well developed, is of key importance in the control of this disease. Rapid diagnostic tests (RDTs) offer great potential to address this need. Reports of significant variation in the field performance of RDTs based on the detection of Plasmodium falciparum histidine-rich protein 2 (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to parasite proteins from geographically distinct P. falciparum isolates, define the epitopes recognized by these MABs, and relate the copy number of the epitopes to MAB reactivity. We observed a significant difference in the reactivity of the same MAB to different isolates and between different MABs tested with single isolates. When the target epitopes of three of the MABs were determined and mapped onto the peptide sequences of the field isolates, significant variability in the frequency of these epitopes was observed. These findings support the role of sequence variation as an explanation for variations in the performance of HRP2-based RDTs and point toward possible approaches to improve their diagnostic sensitivities.

Animals↗

Anti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndrome.

BACKGROUND: The association between a robust or depressed antibody response and clinical severity of SARS remains unknown. OBJECTIVES: To study seroconversion and the magnitude of IgG responses in a SARS cohort with different disease severities. STUDY DESIGN AND METHOD: A retrospective analysis of all acute and convalescent-phase sera collected from a cohort of laboratory-confirmed SARS cases. Anti-SARS-CoV IgG antibody was detected using indirect immunofluorescence technique and quantified by two-fold serial dilutions. Characteristics of patients who seroconverted "early" (<median interval) were compared to those documented to remain sero-negative during the same time interval. Median IgG levels in convalescent-phase sera (collected within 30 days) were compared among patients with different disease severities. Correlations between IgG levels and important laboratory parameters were assessed. RESULTS: A total of 325 laboratory-confirmed SARS cases were analyzed; of which 301 (92.6%) had anti-SARS-CoV IgG detected in their sera at the time of sampling. IgG was first detected on day 4 of illness; seroconversion occurred at a median of 16 days (range 4-35 days), and IgG peak levels were reached in the fourth week. Early seroconversion (<day 16) occurred more frequently among patients who required ICU-admission (chi2; p=0.011). Higher IgG levels were detected in patients who required supplemental oxygen (Mann-Whitney; p=0.002), ICU-admission (p=0.001), had negative pre-discharge fecal RT-PCR results (p=0.004), and lymphopenia at presentation (p=0.028). Peak IgG titres also correlated positively with peak LDH levels (Spearman's r=+0.360; p<0.001) among survivors. CONCLUSIONS: Severe SARS is associated with a more robust IgG response.

Adult↗

Clinical significance of hepatic derangement in severe acute respiratory syndrome.

AIM: Elevation of alanine aminotransferase (ALT) level is commonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS patient. METHODS: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and death. RESULTS: Two hundred and ninety-four patients were included in this study. Seventy (24%) patients had elevated serum ALT on admission and 204 (69%) patients had elevated ALT during the subsequent course of illness. Using peak ALT >5XULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peak ALT >5X ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95%CI 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34 (95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical outcomes. CONCLUSION: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severe hepatitis had worse clinical outcome.

Adolescent↗

Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study.

BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

Adult↗

Temporal-spatial analysis of severe acute respiratory syndrome among hospital inpatients.

BACKGROUND: We report the temporal-spatial spread of severe acute respiratory syndrome (SARS) among inpatients in a hospital ward during a major nosocomial outbreak and discuss possible mechanisms for the outbreak. METHODS: All inpatients who had stayed in the same ward as the initial index case patient for any duration before isolation were recruited into a cohort and followed up to document the occurrence of SARS. The normalized concentration of virus-laden aerosols at different locations of the ward was estimated by use of computational fluid dynamics modeling. The attack rates in the various subgroups stratified by bed location were calculated. Multivariate Cox proportional hazards regression was used to document important risk factors. RESULTS: The overall attack rate of SARS was 41% (30 of 74 subjects). It was 65%, 52%, and 18% in the same bay, adjacent bay, and distant bays, respectively (P = .001). Computation fluid dynamics modeling indicated that the normalized concentration of virus-laden aerosols was highest in the same bay and lowest in the distant bays. Cox regression indicated that staying in the ward on 6 or 10 March entailed higher risk, as well as staying in the same or adjacent bays. The epidemic curve showed 2 peaks, and stratified analyses by bed location suggested >1 generation of spread. CONCLUSIONS: The temporal-spatial spread of SARS in the ward was consistent with airborne transmission, as modeled by use of computational fluid dynamics. Infected health care workers likely acted as secondary sources in the latter phase of the outbreak.

Cohort Studies↗

Severe acute respiratory syndrome: correlation between clinical outcome and radiologic features.

PURPOSE: To evaluate whether there is a correlation between the clinical outcomes and radiologic features of severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: The clinical, laboratory, and radiologic features of 138 patients with SARS were analyzed. Three radiologists in consensus retrospectively assessed the frontal chest radiographs obtained at presentation and during treatment (n = 2045) for the distribution (each lung was divided into upper, middle, and lower zones) and extent of lung parenchymal abnormality. Clinical end points included intensive care unit (ICU) admission and death. RESULTS: Thirty-six (26.1%) patients required ICU care, and eight (5.8%) died. The patients who required ICU care and/or died had more extensive consolidation on chest radiographs obtained initially (median percentage of consolidation, 3.30%, with interquartile range [IR] of 1.70%-8.78% vs 1.70% [IR, 0%-3.30%]; P < .001) and on day 7 after fever onset (median percentage of consolidation, 15.00% [IR, 6.48%-28.73%] vs 5.00% [IR, 2.50%-7.50%]; P < .001) than did surviving patients who did not require ICU care. Patients with involvement of more than one lung zone on initial and day 7 chest radiographs were more likely to require ICU care and/or die than were those with involvement of one or fewer zones (P < .001). Patients with bilateral pneumonic changes at presentation were more likely to have an adverse outcome than were those with unilateral pneumonia (P < .001). Involvement of more than one lung zone at baseline chest radiography was an independent predictor of ICU admission and/or death (odds ratio, 3.16; 95% confidence interval: 1.07, 9.32; P = .037) after adjustments for other significant factors (ie, patient age, and baseline neutrophil count and lactate dehydrogenase level). CONCLUSION: More extensive airspace disease at presentation is an independent predictor of adverse outcome in patients with SARS.

Adult↗

Seroprevalence of antibody to severe acute respiratory syndrome (SARS)-associated coronavirus among health care workers in SARS and non-SARS medical wards.

The seroprevalence of antibody to severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in cohorts of health care workers (HCWs) with subclinical infection in SARS and non-SARS medical wards was 2.3% (3 of 131 HCWs) and 0% (0 of 192 HCWs), respectively. Rates for clinical SARS-CoV infection among 742 HCWs on these wards were highest among nurses (11.6%) and health care assistants (11.8%), indicating that these occupations are associated with the highest risks for exposure.

Antibodies, Viral↗

The spectrum of severe acute respiratory syndrome-associated coronavirus infection.

BACKGROUND: Whether subclinical or atypical presentations of severe acute respiratory syndrome (SARS) occur and whether clinical judgment is accurate in detecting SARS are unknown. OBJECTIVES: To describe the spectrum of SARS coronavirus infection in a large outbreak and to compare diagnoses based on clinical judgment with the SARS coronavirus test. DESIGN: Secondary analysis of prospectively collected clinical data and archived serum. SETTING: A SARS screening clinic of a university hospital in the New Territories of Hong Kong. PATIENTS: 1221 patients attending the clinic between 12 March 2003 and 12 May 2003. MEASUREMENTS: SARS coronavirus serology. RESULTS: 145 of 553 (26%) patients had serologic evidence of SARS coronavirus infection. Of 910 patients who were managed without hospitalization, only 6 had serologic evidence of SARS. Five of the six patients had normal chest radiographs, and four had symptoms such as myalgia, chills, coughing, and feeling feverish. With the SARS coronavirus serologic test as the gold standard, the clinical diagnosis of probable SARS at hospitalization had a sensitivity of 0.96 (95% CI, 0.91 to 0.98) and a specificity of 0.96 (CI, 0.92 to 0.97). LIMITATIONS: Follow-up serologic samples were not obtained from almost half of the patients because they declined further testing. Some people living in the community who were infected but who had minor or no symptoms might not have visited the clinic. CONCLUSIONS: There is little evidence of widespread subclinical or mild forms of SARS coronavirus infection. Clinical diagnoses during the outbreak were reasonable and resulted in appropriate triaging.

Adolescent↗

Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients.

BACKGROUND: The effect of corticosteroid treatment on the viral load of Severe Acute Respiratory Syndrome (SARS) patients is unknown. OBJECTIVE: To compare the plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received early hydrocortisone therapy with those who received placebo. STUDY DESIGN: Serial plasma SARS-CoV RNA concentrations measured in the setting of a prospective, randomized double-blinded, placebo-controlled trial designed to assess the efficacy of "early" (<7 days of illness) hydrocortisone use in previously healthy SARS patients were analyzed. SARS-CoV RNA was quantified using a one-step real-time RT-PCR assay targeting the nucleocapsid gene. RESULTS: Among 16 non-ICU cases, SARS-CoV RNA was detected in plasma since day 3-4 after fever onset; viral concentration peaked in the first week, which then rapidly declined in the second week of illness. On days 8, 12, 16, and 20, the cumulative proportion of patients with undetectable virus in plasma was 31%, 69%, 92%, and 100%, respectively. Plasma SARS-CoV RNA concentrations in the second and third week of illness were significantly higher in patients who received initial hydrocortisone treatment (n = 9), as compared to those who received placebo (n = 7)(AUC; Mann-Whitney, P = 0.023). The median time for SARS-CoV to become undetectable in plasma was 12 days (11-20 days) versus 8 days (8-15 days), respectively. CONCLUSION: Our findings suggested "early" corticosteroid treatment was associated with a higher subsequent plasma viral load.

Adrenal Cortex Hormones↗

Immunofluorescence assay for serologic diagnosis of SARS.

We evaluated an indirect immunofluorescence assay based on virus-infected cells for detecting anti-severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection.

Adolescent↗

Laboratory diagnosis of SARS.

The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription-polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%-40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity.

Adolescent↗

Provider bias in the selection of non-nucleoside reverse transcriptase inhibitor and protease inhibitor-based highly active antiretroviral therapy and HIV treatment outcomes in observational studies.

OBJECTIVE: To compare the characteristics of patients prescribed non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI), and evaluate treatment outcomes in a setting in which nevirapine has been preferentially recommended since 1998. METHODS: A population-based analysis of antiretroviral-naive adults who started highly active antiretroviral therapy (HAART) between 1 August 1996 and 31 July 2000, and who were followed until 31 March 2002. We compared baseline characteristics, and evaluated virological responses and mortality. RESULTS: Overall, 439 patients (28.8%) started HAART with NNRTI (94.1% used nevirapine), 100 (6.6%) used a double PI, and 983 (64.6%) used a single PI-based regimen. Substantial differences were observed between the baseline clinical characteristics of these populations. In adjusted analyses, in comparison with single PI therapy, only the use of NNRTI was associated with more rapid HIV-RNA suppression [relative hazard (RH) 1.42; 95% confidence interval (CI) 1.22-1.65; P < 0.001]. A total of 204 deaths were identified in the study population [42 (9.6%) NNRTI; 11 (11%) double PI; 151 (15.4%) single PI, respectively]. In adjusted analysis, NNRTI (RH 1.01; 95% CI 0.71-1.45) and double PI-based HAART (RH 0.74; 95% CI 0.40-1.39) had similar mortality rates to the single PI reference category. CONCLUSION: NNRTI use was associated with more rapid virological suppression, whereas similar rates of rebound and mortality were found. Nevertheless, major baseline differences existed between patients prescribed the various initial regimens. As such, it is likely that similar selection factors may explain why our findings contrast with several non-randomized studies showing worse clinical outcomes of patients prescribed nevirapine.

Adult↗

Rates of disease progression among human immunodeficiency virus-infected persons initiating multiple-drug rescue therapy.

To characterize survival and to compare rates of disease progression to death of human immunodeficiency virus (HIV)-infected patients, between those initiating multiple-drug rescue therapy (MDRT) and those antiretroviral-inexperienced initiating triple-drug antiretroviral therapy (ART), we conducted a population-based analysis of HIV-infected men and women aged > or =18 years in British Columbia, Canada. Cumulative mortality rates were estimated by use of Kaplan-Meier methods, and Cox-proportional hazard regression was used to model the simultaneous effect of prognostic variables on survival. Cumulative mortality at 36 months was 14.2%+/-2.0% and 10.9%+/-1.0% for the MDRT and triple-drug ART groups, respectively (P=.105, log-rank test). After adjustment for other baseline prognostic variables, MDRT was found not to be a predictor of increased all-cause mortality (relative risk, 1.17; 95% confidence interval, 0.82-1.66) in multivariate analysis. Over the short-term, patients receiving MDRT had relatively low mortality. After adjustment for baseline prognostic factors, rates of survival were comparable with those in patients initiating triple-drug ART.

Adult↗

Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis.

OBJECTIVES: To evaluate the haematological findings of patients with severe acute respiratory syndrome (SARS). DESIGN: Analysis of the demographic, clinical, and laboratory characteristics of patients with SARS. SETTING: Prince of Wales Hospital, Hong Kong. Subjects All patients with a diagnosis of SARS between 11 March and 29 March 2003 who had no pre-existing haematological disorders. MAIN OUTCOME MEASURES: Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed to examine factors associated with adverse outcome. RESULTS: 64 male and 93 female patients were included in this study. The most common findings included lymphopenia in 153 (98%) of the 157 patients, neutrophilia in 129 (82%), thrombocytopenia in 87 patients (55%), followed by thrombocytosis in 77 (49%), and isolated prolonged activated partial thromboplastin time in 96 patients (63%). The haemoglobin count dropped by more than 20 g/l from baseline in 95 (61%) patients. Four patients (2.5%) developed disseminated intravascular coagulation. Lymphopenia was shown in haemato-lymphoid organs at postmortem examination. Multivariate analysis showed that advanced age and a high concentration of lactate dehydrogenase at presentation were independent predictors of an adverse outcome. Subsets of peripheral blood lymphocytes were analysed in 31 patients. The counts of CD4 positive and CD8 positive T cells fell early in the course of illness. Low counts of CD4 and CD8 cells at presentation were associated with adverse outcomes. CONCLUSIONS: Abnormal haematological variables were common among patients with SARS. Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity.

Blood Coagulation↗